My research interests focus on developing experimental strategies for brain rescue and repair. As a potential therapy for treatment of neurodegenerative diseases, stem cells and neural progenitor cells (NPCs) have been proposed as unique sources of transplantable cells to provide neuroprotection to the remaining nervous system elements and to replace degenerating neurons and glia. We are using this strategy and are evaluating the survival, differentiation and integration of NPCs and stem cells transplanted into normal and damaged rodent retinas used as models of retinal degeneration and glaucoma. In addition to cell replacement, another powerful application for stem cells in the retina is gene delivery. For example, neurotrophic factors are known to have protective effects on damaged neurons that would otherwise not survive. Engineering stem cells to serve as vehicles for delivery of neurotrophic factors is a novel and exciting approach as a treatment strategy for blinding ocular diseases and other neurodegenerative disorders (including traumatic brain injury and nerve regeneration). In addition to NPCs, the multipotent nature of bone marrow-derived stem cells (MSCs) makes them attractive candidates for cell-based therapies. We have genetically engineered MSCs to produce and secrete bioactive neurotrophic factors for delivery to the injured CNS. Moreover, the MSCs may be used for autologous transplantation and therefore minimize the likelihood of immune rejection of the grafted cells. Engineering stem cells ex vivo for retinal repair strategies may ultimately provide a reliable means of long-term delivery of therapeutic factors.

Another research focus of the Sakaguchi lab is using integrative neuroprotective and neuroregenerative strategies to study peripheral nerve regeneration and traumatic brain injury. This research aims to develop experimental strategies to repair the damaged nervous system using biomaterials and biodegradable polymers; bioactive molecules; and stem cells.